Background Chronic mucosal irritation, by for instance smoking or periodontitis-associated microbes, has been suggested to be a key etiological trigger in anti-citrullinated protein antibody (ACPA) positive arthritis. Although circulating IgA-ACPAs, which are mainly monomeric, may associate with a worse disease course, the importance of dimeric secretory IgA- (sIgA-) ACPA at mucosal surfaces remains poorly defined. Levels of sIgA-ACPA in serum could possibly reflect ongoing immune responses to citrullinated proteins at mucosal surfaces, allowing for more convenient analyses than using mucosal fluids.
Objectives To investigate whether sIgA-ACPA occurs in serum from patients with rheumatoid arthritis (RA), and to determine its relationship to disease severity, smoking, dental health, and levels of salivary IgA-ACPA.
Methods Patients with established RA (n=113) were recruited at the rheumatology clinic of Falun Hospital, Sweden. Sampling of serum, saliva and clinical measures were collected at the same occasion. Disease activity was assessed by the 28-joint disease activity score (DAS28), functional ability by the Health Assessment Questionnaire (HAQ), and radiographic joint damage by chart reviews. Dental health and smoking habits were assessed by a questionnaire. ACPAs were detected by enzyme-linked immunoassays (ELISAs) using anti-CCP (aCCP) kits (EuroDiagnostica, Malmö, Sweden) with exchange of detection antibodies to polyclonal goat anti-secretory component for sIgA-aCCP, and polyclonal rabbit anti-human α-chain for IgA-aCCP. 46 blood donors served as controls. The cutoff for positive serum sIgA-aCCP test was set to 50 arbitrary units (AU)/mL, corresponding to >99th percentile of the controls. In saliva, IgA-aCCP was considered positive when the optical density ratio to the corresponding arginine peptide was > 1.5.
Results The proportion of patients testing positive for aCCP in serum was 76% for IgG, 43% for IgA, and 26% for sIgA. All patients with a positive IgA-aCCP or sIgA-aCCP test also had IgG-aCCP. At the time of sampling, patients positive for sIgA-aCCP had higher mean DAS28 levels than sIgA-aCCP negative patients (3.7 vs 2.6, respectively, P=0.001), and higher mean HAQ (0.99 vs 0.67, P=0.042). IgA-aCCP in serum showed similar differences, but DAS28 remained higher among sIgA-aCCP positives also when analyzing IgA-aCCP positive patients alone (P=0.01). Regarding IgG-aCCP, no differences were found. Patients testing positive for IgA-aCCP in saliva had higher mean DAS28 (3.7 vs 2.8, P=0.049), while none of the IgA class aCCP tests associated with the presence of joint erosions. All aCCP tests were more often positive among ever smokers, but did not differ according to dental health.
Conclusions Circulating sIgA-ACPA occur in RA, and associates with a more aggressive disease at the time of sampling. IgA-aCCP levels in serum and saliva also associate with a higher DAS28 score. As no such difference was seen regarding IgG-aCCP, these findings may suggest that ongoing immune responses to citrullinated proteins at mucosal surfaces contribute to joint inflammation in RA. Prospective data is underway.
Disclosure of Interest None Declared
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